Dataset Information

Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study.

ABSTRACT:

Introduction

Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype.

Methods

Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments.

Results

Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations.

Discussion

This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients.

Highlights

This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

SUBMITTER: Ulugut H

PROVIDER: S-EPMC11350044 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study.

Ulugut Hulya H Bertoux Maxime M Younes Kyan K Montembeault Maxime M Fumagalli Giorgio G GG Samanci Bedia B Illán-Gala Ignacio I Kuchcinski Gregory G Leroy Melanie M Thompson Jennifer C JC Kobylecki Christopher C Santillo Alexander F AF Englund Elisabet E Waldö Maria Landqvist ML Riedl Lina L Van den Stock Jan J Vandenbulcke Mathieu M Vandenberghe Rik R Laforce Robert R Ducharme Simon S Pressman Peter S PS Caramelli Paulo P de Souza Leonardo Cruz LC Takada Leonel T LT Gurvit Hakan H Hansson Oskar O Diehl-Schmid Janine J Galimberti Daniela D Pasquier Florence F Miller Bruce L BL Scheltens Philip P Ossenkoppele Rik R van der Flier Wiesje M WM Barkhof Frederik F Fox Nick C NC Sturm Virginia E VE Miyagawa Toji T Whitwell Jennifer L JL Boeve Bradley B Rohrer Jonathan D JD Gorno-Tempini Maria Luisa ML Josephs Keith A KA Snowden Julie J Warren Jason D JD Rankin Katherine P KP Pijnenburg Yolande A L YAL

Alzheimer's & dementia : the journal of the Alzheimer's Association 20240710 8

<h4>Introduction</h4>Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype.<h4>Methods</h4>Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments.<h4>Results</h4>Common symptoms included mental rigidity/preoc ...[more]

PMID: 38982845

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Project description:Focal anterior temporal lobe degeneration often preferentially affects the left or right hemisphere. While patients with left-predominant anterior temporal lobe atrophy show severe anomia and verbal semantic deficits and meet criteria for semantic variant primary progressive aphasia and semantic dementia, patients with early right anterior temporal lobe atrophy are more difficult to diagnose as their symptoms are less well understood. Focal right anterior temporal lobe atrophy is associated with prominent emotional and behavioural changes, and patients often meet, or go on to meet, criteria for behavioural variant frontotemporal dementia. Uncertainty around early symptoms and absence of an overarching clinico-anatomical framework continue to hinder proper diagnosis and care of patients with right anterior temporal lobe disease. Here, we examine a large, well-characterized, longitudinal cohort of patients with right anterior temporal lobe-predominant degeneration and propose new criteria and nosology. We identified individuals from our database with a clinical diagnosis of behavioural variant frontotemporal dementia or semantic variant primary progressive aphasia and a structural MRI (n = 478). On the basis of neuroimaging criteria, we defined three patient groups: right anterior temporal lobe-predominant atrophy with relative sparing of the frontal lobes (n = 46), frontal-predominant atrophy with relative sparing of the right anterior temporal lobe (n = 79) and left-predominant anterior temporal lobe-predominant atrophy with relative sparing of the frontal lobes (n = 75). We compared the clinical, neuropsychological, genetic and pathological profiles of these groups. In the right anterior temporal lobe-predominant group, the earliest symptoms were loss of empathy (27%), person-specific semantic impairment (23%) and complex compulsions and rigid thought process (18%). On testing, this group exhibited greater impairments in Emotional Theory of Mind, recognition of famous people (from names and faces) and facial affect naming (despite preserved face perception) than the frontal- and left-predominant anterior temporal lobe-predominant groups. The clinical symptoms in the first 3 years of the disease alone were highly sensitive (81%) and specific (84%) differentiating right anterior temporal lobe-predominant from frontal-predominant groups. Frontotemporal lobar degeneration-transactive response DNA binding protein (84%) was the most common pathology of the right anterior temporal lobe-predominant group. Right anterior temporal lobe-predominant degeneration is characterized by early loss of empathy and person-specific knowledge, deficits that are caused by progressive decline in semantic memory for concepts of socioemotional relevance. Guided by our results, we outline new diagnostic criteria and propose the name, 'semantic behavioural variant frontotemporal dementia', which highlights the underlying cognitive mechanism and the predominant symptomatology. These diagnostic criteria will facilitate early identification and care of patients with early, focal right anterior temporal lobe degeneration as well as in vivo prediction of frontotemporal lobar degeneration-transactive response DNA binding protein pathology.

Project description:Inappropriate social behaviours are early and distinctive symptoms of the temporal and frontal variants of frontotemporal lobar degeneration (FTLD). Knowledge of social behaviour is essential for appropriate social conduct. It is unknown, however, in what way this knowledge is degraded in FTLD. In a recent functional MRI study, we have identified a right-lateralized superior anterior temporal lobe (aTL) region showing selective activation for 'social concepts' (i.e. concepts describing social behaviour: e.g. 'polite', 'stingy') as compared with concepts describing less socially relevant animal behaviour ('animal function concepts': e.g. 'trainable', 'nutritious'). In a further fMRI study, superior aTL activation was independent of the context of actions and feelings associated with these social concepts. Here, we investigated whether the right superior sector of the aTL is necessary for context-independent knowledge of social concepts. We assessed neuronal glucose uptake using 18-fluoro-deoxy-glucose-positron emission tomography (FDG-PET) and a novel semantic discrimination task which probed knowledge of social and animal function concepts in patients with FTLD (n = 29) and corticobasal syndrome (n = 18). FTLD and corticobasal syndrome groups performed equally poorly on animal function concepts but FTLD patients showed more pronounced impairments on social concepts than corticobasal syndrome patients. FTLD patients with right superior aTL hypometabolism, as determined on individual ROI analyses, were significantly more impaired on social concepts than on animal function concepts. FTLD patients with selective impairments for social concepts, as determined on individual neuropsychological profiles, showed higher levels of inappropriate social behaviours ('disinhibition') and demonstrated more pronounced hypometabolism in the right superior aTL, the left temporal pole and the right lateral orbitofrontal and dorsomedial prefrontal cortex as compared with FTLD patients showing selective impairments of animal function concepts. Combining both FTLD subgroup analyses, based on anatomical and neuropsychological criteria, by using inclusive masks, revealed the right superior aTL as associated with selective impairments of social concepts in both analyses. These results corroborate the hypothesis that the right aTL is necessary for representing conceptual social knowledge. Further, we provide first evidence for the potential importance of conceptual social knowledge impairments as contributing to behavioural symptoms of FTLD.

Project description:The concept of the right temporal variant of frontotemporal dementia (rtvFTD) is still equivocal. The syndrome accompanying predominant right anterior temporal atrophy has previously been described as memory loss, prosopagnosia, getting lost and behavioural changes. Accurate detection is challenging, as the clinical syndrome might be confused with either behavioural variant FTD (bvFTD) or Alzheimer's disease. Furthermore, based on neuroimaging features, the syndrome has been considered a right-sided variant of semantic variant primary progressive aphasia (svPPA). Therefore, we aimed to demarcate the clinical and neuropsychological characteristics of rtvFTD versus svPPA, bvFTD and Alzheimer's disease. Moreover, we aimed to compare its neuroimaging profile against svPPA, which is associated with predominant left anterior temporal atrophy. Of 619 subjects with a clinical diagnosis of frontotemporal dementia or primary progressive aphasia, we included 70 subjects with a negative amyloid status in whom predominant right temporal lobar atrophy was identified based on blinded visual assessment of their initial brain MRI scans. Clinical symptoms were assessed retrospectively and compared with age- and sex-matched patients with svPPA (n = 70), bvFTD (n = 70) and Alzheimer's disease (n = 70). Prosopagnosia, episodic memory impairment and behavioural changes such as disinhibition, apathy, compulsiveness and loss of empathy were the most common initial symptoms, whereas during the disease course, patients developed language problems such as word-finding difficulties and anomia. Distinctive symptoms of rtvFTD compared to the other groups included depression, somatic complaints, and motor/mental slowness. Aside from right temporal atrophy, the imaging pattern showed volume loss of the right ventral frontal area and the left temporal lobe, which represented a close mirror image of svPPA. Atrophy of the bilateral temporal poles and the fusiform gyrus were associated with prosopagnosia in rtvFTD. Our results highlight that rtvFTD has a unique clinical presentation. Since current diagnostic criteria do not cover specific symptoms of the rtvFTD, we propose a diagnostic tree to be used to define diagnostic criteria and call for an international validation.

Project description:Degraded semantic memory is a prominent feature of frontotemporal dementia (FTD). It is classically associated with semantic dementia and anterior temporal lobe (ATL) atrophy, but semantic knowledge can also be compromised in behavioural variant FTD. Motivated by understanding behavioural change in FTD, recent research has focused selectively on social-semantic knowledge, with proposals that the right ATL is specialized for social concepts. Previous studies have assessed very different types of social concepts and have not compared performance with that of matched non-social concepts. Consequently, it remains unclear to what extent various social concepts are (i) concurrently impaired in FTD, (ii) distinct from general semantic memory and (iii) differentially supported by the left and right ATL. This study assessed multiple aspects of social-semantic knowledge and general conceptual knowledge across cohorts with ATL damage arising from either neurodegeneration or resection. We assembled a test battery measuring knowledge of multiple types of social concept. Performance was compared with non-social general conceptual knowledge, measured using the Cambridge Semantic Memory Test Battery and other matched non-social-semantic tests. Our trans-diagnostic approach included behavioural variant FTD, semantic dementia and 'mixed' intermediate cases to capture the FTD clinical spectrum, as well as age-matched healthy controls. People with unilateral left or right ATL resection for temporal lobe epilepsy were also recruited to assess how selective damage to the left or right ATL impacts social- and non-social-semantic knowledge. Social- and non-social-semantic deficits were severe and highly correlated in FTD. Much milder impairments were found after unilateral ATL resection, with no left versus right differences in social-semantic knowledge or general semantic processing and with only naming showing a greater deficit following left versus right damage. A principal component analysis of all behavioural measures in the FTD cohort extracted three components, interpreted as capturing (i) FTD severity, (ii) semantic memory and (iii) executive function. Social and non-social measures both loaded heavily on the same semantic memory component, and scores on this factor were uniquely associated with bilateral ATL grey matter volume but not with the degree of ATL asymmetry. Together, these findings demonstrate that both social- and non-social-semantic knowledge degrade in FTD (semantic dementia and behavioural variant FTD) following bilateral ATL atrophy. We propose that social-semantic knowledge is part of a broader conceptual system underpinned by a bilaterally implemented, functionally unitary semantic hub in the ATLs. Our results also highlight the value of a trans-diagnostic approach for investigating the neuroanatomical underpinnings of cognitive deficits in FTD.

Dataset Information

Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study.

Introduction

Methods

Results

Discussion

Highlights

Publications

Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study.

Similar Datasets

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